Endocannabinoid system modulator use in everyday clinical practice in the UK and Spain.

“Spasticity is a disabling complication of multiple sclerosis. Some commonly used oral medications include baclofen, tizanidine, anticonvulsants and benzodiazepines, but their benefits are modest.

Sativex(®) (GW Pharmaceuticals PLC, Porton Down, UK; Laboratorios Almirall, SA, Barcelona, Spain) is a unique cannabinoid-based medicine with two main active ingredients; 9-δ-tetrahydrocannabinol, which acts mainly on cannabinoid 1 receptors in the CNS and plays a key role in the modulation of spasticity and spasms, and cannabidiol, which has different properties, including minimization of the psychoactivity associated with 9-δ-tetrahydrocannabinol. Sativex is indicated for symptomatic improvement in adult patients with moderate-to-severe multiple sclerosis-related spasticity who have not responded adequately to other first- or second-line antispasticity medications, and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy.

Over the past couple of years, Sativex has been approved for use in a number of European countries and ongoing postmarketing studies are evaluating the possible risks associated with Sativex treatment by systematically collecting all suspected adverse reactions that occur in patients from the start of treatment. Interim data from the UK as well as Spanish Sativex safety registries confirm that clinical benefit is maintained over the longer term despite the expected trend for deterioration owing to disease progression.

 Even after more than 2 years of use, no new safety/tolerability signals have emerged with Sativex, including no evidence of driving impairment and no relevant incidence of falls or other adverse events of concern, such as psychiatric or nervous system events.

Sativex appears to be a well-tolerated and useful add-on therapy in patients who have not achieved an adequate response with traditional antispastic agents.”

http://www.ncbi.nlm.nih.gov/pubmed/23369054

The endocannabinoid system is dysregulated in multiple sclerosis and in experimental autoimmune encephalomyelitis

“The ability of cannabinoids to modulate both inflammatory and degenerative neuronal damage prompted investigations on the potential benefits of such compounds in multiple sclerosis (MS) and in animal models of this disorder. Here we measured endocannabinoid levels, metabolism and binding, and physiological activities in 26 patients with MS (17 females, aged 19–43 years), 25 healthy controls and in mice with experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS.

 Our results show that MS and EAE are associated with significant alterations of the endocannabinoid system. We found that anandamide (AEA), but not 2-arachidonoylglycerol (2-AG), was increased in the CSF of relapsing MS patients. AEA concentrations were also higher in peripheral lymphocytes of these patients, an effect associated with increased synthesis and reduced degradation of this endocannabinoid. Increased synthesis, reduced degradation, and increased levels of AEA were also detected in the brains of EAE mice in the acute phase of the disease, possibly accounting for its anti-excitotoxic action in this disorder. Accordingly, neurophysiological recordings from single neurons confirmed that excitatory transmission in EAE slices is inhibited by CB1 receptor activation, while inhibitory transmission is not.

Our study suggests that targeting the endocannabinoid system might be useful for the treatment of MS.”

http://brain.oxfordjournals.org/content/130/10/2543.abstract

Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease.

“Inflammatory bowel disease (IBD) is an incurable disease which affects millions of people in industrialised countries. Anecdotal and scientific evidence suggest that Cannabis use may have a positive impact in IBD patients.

 Here, we investigated the effect of cannabigerol (CBG), a non-psychotropic Cannabis-derived cannabinoid, in a murine model of colitis…

  In conclusion, CBG attenuated murine colitis, reduced nitric oxide production in macrophages (effect being modulated by the CB(2) receptor) and reduced ROS formation in intestinal epithelial cells.

CBG could be considered for clinical experimentation in IBD patients.”

http://www.ncbi.nlm.nih.gov/pubmed/23415610

Activation of Cannabinoid CB2 Receptor-Mediated AMPK/CREB Pathway Reduces Cerebral Ischemic Injury.

“The type 2 cannabinoid receptor (CB2R) was recently shown to mediate neuroprotection in ischemic injury. However, the role of CB2Rs in the central nervous system, especially neuronal and glial CB2Rs in the cortex, remains unclear. We, therefore, investigated anti-ischemic mechanisms of cortical CB2R activation in various ischemic models….

  Collectively, these data demonstrate that cortical CB2R activation by TC (trans-caryophyllene, a CB2R agonist,), ameliorates ischemic injury, potentially through modulation of AMPK/CREB signaling, and suggest that cortical CB2Rs might serve as a putative therapeutic target for cerebral ischemia.”

http://www.ncbi.nlm.nih.gov/pubmed/23414569

Medical cannabis relieves sufferers of chronic ailments

“Treatment can improve appetite, ease chronic pain, and more, say TAU researchers. Though controversial, medical cannabis has been gaining ground as a valid therapy, offering relief to suffers of diseases such as cancer, Post-Traumatic Stress Disorder, ALS and more. The substance is known to soothe severe pain, increase the appetite, and ease insomnia where other common medications fail.”

More: http://www.virtualmedicalcentre.com/news/medical-cannabis-relieves-sufferers-of-chronic-ailments/18330

Pot patch considered medical breakthrough

“Advocates are fighting to legalize marijuana. The University of Mississippi has the only legally grown marijuana crop in the nation.Faculty members and student researchers have now developed a new patch that could potentially provide help to patients who need it.

The patch developed at Ole Miss could help patients overcome problems associated with taking the drug in pill form. The patch is placed above the gum line.

“In addition to pain, it will include things like reducing intraocular pressure and therefore would be good for glaucoma. [It] will be good for alleviating the nausea and vomiting associated with chemotherapy; it would also be good for appetite stimulation for patients suffering from the syndrome, anti-inflammatory activity, anti-anxiety,” explains Dr. ElSohly.”

More: http://www.myfoxal.com/story/21116615/pot-patch-offers-medicinal-marijuana-treatment-at-ole-miss

Ole Miss cooks up marijuana pain patch

“(WMC-TV) – Ole Miss is home to the only legally grown marijuana crop in the nation and a new development there is creating quite a buzz. Faculty and student researchers say they created a new pain reliever in the form of a patch.

Dr. Mahmoud Elsohly is a faculty member at the School of Pharmacy at Ole Miss. He and his team have been working inside their marijuana research lab for nearly seven years to find alternative uses for THC, which is the main psychoactive ingredient in marijuana.

“The plant itself has a great potential for good medicine coming out of the Cannabis plant…”

More: http://www.14news.com/story/21217891/a-look-ahead-ole-miss-cooks-up-marijuana-pain-patch

Cannabis could provide relief for Parkinson’s pain

Woman smokes a marijuana cigarette [illustrative]

“As many as eight out of every 10 of those with Parkinson’s disease suffer from inexplicable pains that until now have been left untreated because they were thought to be an inevitable part of the progressive and eventually fatal neurological disease. Parkinson’s, a brain disorder that leads to tremors and difficulty with walking, coordination and movement, usually develops after age 50 and is one of the most common nervous system disorders of the elderly.But new research at the Rabin Medical Center- Beilinson Campus has found that genetic factors explain such Parkinson’s pain, and that the new understanding will make unique treatments possible. Eight genes known to be involved in pain were examined in 237 Parkinson’s patients, according to a research paper published recently in the European Journal of Pain, and the observed variations were connected to functions of cannabis-like substances (cannabinoids) in the brain.

Research project head Prof. Ruth Djaldetti, a senior physician in the neurology department and head of the movement disorders clinic, said that the results support the treatment of Parkinson’s patients with medical marijuana.

Djaldetti encourages more research into the use of cannabis for pain relief.

There are some 20,000 people with Parkinson’s in Israel, and about 50 percent to 80% of them suffer from this previously unexplained and untreated pain. Djaldetti expects that in the future, gene mapping will make it possible to suit personalized medication to these patients.”

 

Cannabis and Δ(9)-tetrahydrocannabinol (THC) for weight loss?

“Obesity is one of the highest preventable causes of morbidity and mortality in the developed world. It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the ‘munchies’).

This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome. This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB(1) receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile. Despite being efficacious, Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market.

We recently discovered that the prevalence of obesity is paradoxically much lower in cannabis users as compared to non-users and that this difference is not accounted for by tobacco smoking status and is still present after adjusting for variables such as sex and age.

 Here, we propose that this effect is directly related to exposure to the Δ(9)-tetrahydrocannabinol (THC) present in cannabis smoke. We therefore propose the seemingly paradoxical hypothesis that THC or a THC/cannabidiol combination drug may produce weight loss and may be a useful therapeutic for the treatment of obesity and its complications.”

http://www.ncbi.nlm.nih.gov/pubmed/23410498

Pot Fights Breast Cancer

“For years, cancer patients have used pot to combat the side effects of chemotherapy. But evidence has grown, both clinical and anecdotal, that cannabis has the potential to impede the spread of cancer itself. 

Now, researchers in Japan are reporting that CBDA keeps breast cancer cells from spreading. 

CBD, the miracle of component of cannabis that has been shown to have profound efficacy as a pain reliever, is obtained from its parent molecule, cannabidiolic acid or CBDA.

Until now, investigators have wondered whether CBDA is biologically active. But the study reports: “CBDA is an inhibitor of highly aggressive human breast cancer cell migration.””-

by Dan Skye

http://hightimes.com/news/dskye/7912

More: http://www.sciencedirect.com/science/article/pii/S0378427412012854